Project Summary/Abstract Opioid overuse, injection drug use, and overdose have become a national public health crisis, with over 60,000 drug overdose deaths in 2016 in the US, most involving opioids. Our objective is to conduct model-based studies that estimate the epidemiologic consequences of opioid use on HIV and HCV, including the benefits, harms, and resource use of opioid prevention and mitigation strategies. We will assess how best to reduce the incidence of HIV and HCV associated with opioid use and to improve quality of life for people with co- occurring HIV or HCV and opioid use disorder. Our aims are to: 1. Model the effect of the opioid epidemic on transmission of HIV and HCV. We will model the implications of the opioid epidemic on HIV and HCV incidence, prevalence, concentration in subpopulations, gender- and race-based differences. 2. Model the epidemiologic and population impacts of individual strategies to prevent and mitigate the harms of opioids and drug injection on HIV and HCV outcomes. We will evaluate prevention strategies including adaptive screening for HIV and HCV to aid in outbreak and hotspot identification, changing prescribing practices and monitoring programs, HIV pre-exposure prophylaxis (PrEP), intensive HIV and HCV screening, and mitigation strategies including medications for addiction treatment, psychosocial interventions, and distribution of naloxone. 3. Model the epidemiologic and population impact of portfolios of strategies to mitigate the harms of opioid use and drug injection on HIV and HCV outcomes. Because no single strategy will likely have sufficient impact on population health outcomes, we will examine sets of the strategies described in Aim 2 to assess which combinations have the potential for the largest epidemiologic impact on morbidity and mortality. 4. Model the impact of barriers to implementation of effective strategies and portfolios of strategies to reduce the harms of opioid use on HIV and HCV. We will model the effects of barriers to implementation steps (e.g., recruitment, referral, participation, and retention) for strategies identified in Aims 2 and 3. The proposed work will provide clinicians and policymakers with critically needed guidance about how combinations of strategies can efficiently mitigate the national public health crisis from opioid use and how such interventions can be integrated to reduce incidence of HIV and HCV and to improve both length and quality of life for people with HIV, HCV, and opioid use.